Description: (Applicant?s Description)The general goal of this program is directed at gaining a deeper understanding of the molecular mechanisms which are the basis for the normal tissue late effects which are observed in the lung following radiation. Previous CERRIS programs have led to the paradigm of radiation late effects being dependent upon the "conversation" which takes place between a number of injured cells, rather than the classic concept of a single target cell. In pursuit of this goal, they mean to further define the conversation, which they have hypothesized as a "cytokine cascade", in terms of the spatial and temporal release of proinflammatory and profibrotic cytokines and growth factors, and their genetic context. Expansion of this paradigm has led them to postulate the role of the immune system in the development of late tissue effects and this will be explored in more detail. Modulation of the cytokine cascade(s) and/or the immune system will be investigated as a means of both elucidating the roles of specific cytokines, as well as suggesting routes of amelioration.